Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell-surface in human adipocytes: increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents

Context:Immunosuppressive agentes are associated with profound metabolic side effects including new-onset diabetes and dyslipidemia after organ transplantation. Objective: Toi nvestigated the effects of the cyclosporine A(CsA)or tacrolimus ong lucose uptake and insulin signalling in human adipocytes and their impact on the regulation of celular trafficking of the glucose transporter 4 (GLUT4). Design:Human isolated adipocytes were incubated with therapeutic concentrations of either CsA or tacrolimus, and glucose uptake and expression of insulin signaling proteins were assessed. Furthermore,we studied effects of CsA and tacrolimus on the regulation of celular trafficking of the GLUT4 in differentiated human pre-adipocytes and L6 cells. Results:CsA and tacrolimus had a concentration-dependent inhibitory effect on basal and insulin stimulated 14C-glucose uptake in adipocytes. Although phosphorylation at Tyr1146 of insulin receptor (IR) was inhibited by tacrolimus, the phosphorylation and/or protein levels of the insulin signalling proteinsIRS1/2,p85-PI3K,PKB,AS160 and mTORC1,as well as GLUT4 and GLUT1,were unchanged by CsA or tacrolimus. Furthermore, CsA and tacrolimus reduced the GLUT4 amount localized at the cell surfasse of differentiated human pre-adipocytes and L6 cells in the presence of insulin.This occurred by na increased rate of GLUT4 endocytosis,with no change in the exocytosis rate. Conclusions: These results suggest that therapeutic concentrations of CsA and tacrolimus can inhibit glucose uptake independente of insulin signalling by removing GLUT4 from the cell surface via na increased rate of endocytosis.Such mechanisms can contribute to the development of insulin resistance and diabetes associated with immunosuppressive therapy.In addition,they may provide novel pharmacological approaches for treatment of diabetes

Individuals and Multilevel Management: A Study of the Perceived Adaptive Capacity of the Goose Management System among Farmers in Sweden

Agricultural damage by geese is a growing problem in Europe and farmers play a key role in the emerging multilevel adaptive management system. This study explored how characteristics associated with the farmer and the farm, along with experience of damage, cognitive appraisals, emotions, and management beliefs were associated with the perceived adaptive capacity of the goose management system among farmers in the south of Sweden (n = 1,067). Survey results revealed that owning a larger farm, a farm closer to water or formally protected areas, along with cultivating cereal and root crops, were associated with geese evoking stronger negative emotions. Further, more previous experience of damage was related to stronger negative emotions and lower levels of perceived adaptive capacity. However, even more important determinants of perceived adaptive capacity were cognitive appraisals, emotions, and management beliefs. Bridging the ties between individual farmers and the system is important for improved multilevel management

Interlaboratory comparison to evaluate the methodology for determination of the media filtration efficiency against nanoparticles

Current international standards dealing with efficiency test for filters and filter media focus on measurement of the minimum efficiency at the most penetrating particle size. The available knowledge and instruments provide a solid base for development of test methods to determine the effectiveness of filtration media against airborne nanoparticles down to single-digit nanometer range. An interlaboratory evaluation was performed in the framework of the European Mandate M/461 activities, within the Technical Committee 195 of European Committee for Standardization (CEN/TC195). The purpose was to develop a methodology to determine effectiveness of filtration media against air-borne particles in the 3 – 500 nm range. Five different laboratories (Camfil, ETH/Empa, Politecnico di Torino, University of Minnesota, Unifil) participate in the round robin test in order to verify the repeatability and reproducibility of the test method. The qualification of test rig and apparatus was performed prior of the filtration efficiency and air flow resistance measurement tests.Twilled dutch weave wire mesh was chosen to perform the validation filtration efficiency tests so as to ensure high uniformity of the samples being tested by each different laboratory. We present the experimental data with the discussion about their validity

Mental, Physical and Social Functioning in Independently Living Senior House Residents and Community-Dwelling Older Adults

Senior houses provide social interaction and support, potentially supporting older people’s physical and mental functioning. Few studies have investigated functioning of senior house residents. The aim was to compare functioning between senior house residents and community-dwelling older adults in Finland. We compared senior house residents (n = 336, 69% women, mean age 83 years) to community-dwelling older adults (n = 1139, 56% women, mean age 74 years). Physical and mental functioning were assessed using the SF 36-Item Health Survey. Loneliness and frequency of social contacts were self-reported. The analyses were adjusted for age, socioeconomic factors and diseases. Physical functioning was lower among men in senior houses compared to community-dwelling men (mean 41.1 vs. 46.4, p = 0.003). Mental functioning or the frequency of social contacts did not differ between type of residence in either sex. Loneliness was higher among women in senior houses compared to community-dwelling women (OR = 1.67, p = 0.027). This was not observed in men. Results suggest that women in senior houses had similar physical and mental functioning compared to community-dwelling women. Male senior house residents had poorer physical functioning compared to community-dwelling men. Women living in senior houses were lonelier than community-dwelling women despite the social environment

Mental, Physical and Social Functioning in Independently Living Senior House Residents and Community-Dwelling Older Adults

Senior houses provide social interaction and support, potentially supporting older people’s physical and mental functioning. Few studies have investigated functioning of senior house residents. The aim was to compare functioning between senior house residents and community-dwelling older adults in Finland. We compared senior house residents (n = 336, 69% women, mean age 83 years) to community-dwelling older adults (n = 1139, 56% women, mean age 74 years). Physical and mental functioning were assessed using the SF 36-Item Health Survey. Loneliness and frequency of social contacts were self-reported. The analyses were adjusted for age, socioeconomic factors and diseases. Physical functioning was lower among men in senior houses compared to community-dwelling men (mean 41.1 vs. 46.4, p = 0.003). Mental functioning or the frequency of social contacts did not differ between type of residence in either sex. Loneliness was higher among women in senior houses compared to community-dwelling women (OR = 1.67, p = 0.027). This was not observed in men. Results suggest that women in senior houses had similar physical and mental functioning compared to community-dwelling women. Male senior house residents had poorer physical functioning compared to community-dwelling men. Women living in senior houses were lonelier than community-dwelling women despite the social environment

Pharmacological basis and clinical evidence of dabigatran therapy

Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves

Antonovsky’s Sense of Coherence Scale: Cultural Validation of Soc Questionnaire and Socio-Demographic Patterns in an Italian Population

BACKGROUND: The theory of salutogenesis entails that the ability to use resources for one's wellbeing is more important than the resources themselves. This ability is referred to as the Sense of Coherence (SOC). This paper present the cross-culturally adapted version of the Italian questionnaire (13 items), and the psychometric and statistical testing of the SOC properties. It offers for the first time a view of the distribution of SOC in an Italian sample, and uses a multivariate method to clarify the effects of socio-demographic determinants on SOC. METHODS: The cross-cultural adaptation of the English SOC questionnaire was carried out according to the guidelines reported in literature. To evaluate the psychometric and statistical properties we assessed reliability, validity and frequency distribution of the collected data. A Generalised Linear Model was used to analyse the effects of socio demographic variables on SOC. RESULTS: The Italian SOC scale demonstrates a good internal consistency (α = 0.825). The model obtained with factorial analysis is not related to the traditional dimensions of SOC represented in more than one factor. The multivariate analysis highlights the joint influence of gender, age and education on SOC. CONCLUSION: The validated Italian questionnaire is now available. Socio-demographic variables should be taken into account as confounders when SOC values among different populations are compared. Presenting data on SOC of the Italian population makes a control population available for comparisons with specific subgroups, such as patient populations. Now, the Italian challenge is to integrate the salutogenic approach into Public Health police

Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis

Map based cloning in Arabidopsis thaliana can be a difficult and time-consuming process, specifically if the phenotype is subtle and scoring labour intensive. Here, we have re-sequenced the 120-Mb genome of a novel Arabidopsis clock mutant early bird (ebi-1) in Wassilewskija (Ws-2). We demonstrate the utility of sequencing a backcrossed line in limiting the number of SNPs considered. We identify a SNP in the gene AtNFXL-2 as the likely cause of the ebi-1 phenotype

Body composition as a predictor of physical performance in older age : A ten- year follow-up of the Helsinki Birth Cohort Study

Background: This study assessed how different measures of body composition predict physical performance ten years later among older adults. Methods: The participants were 1076 men and women aged 57 to 70 years. Body mass index (BMI), waist circumference, and body composition (bioelectrical impedance analysis) were measured at baseline and physical performance (Senior Fitness Test) ten years later. Linear regression analyses were adjusted for age, education, smoking, duration of the follow-up and physical activity. Results: Greater BMI, waist circumference, fat mass, and percent body fat were associated with poorer physical performance in both sexes (standardized regression coefficient [beta] from -0.32 to -0.40, p <0.001). Lean mass to BMI ratio was positively associated with later physical performance (beta = 0.31 in men, beta = 0.30 in women, p <0.001). Fat-free mass index (lean mass/height(2)) in both sexes and lean mass in women were negatively associated with later physical performance. Lean mass residual after accounting for the effect of height and fat mass was not associated with physical performance. Conclusions: Among older adults, higher measures of adiposity predicted poorer physical performance ten years later whereas lean mass was associated with physical performance in a counterintuitive manner. The results can be used when appraising usefulness of body composition indicators for definition of sarcopenic obesity.Peer reviewe